The present invention relates to a plurality of novel processes and novel intermediates for preparing 3-(1-hydroxyphenyl-1-alkoximinomethyl)dioxazines, which are known as intermediates for preparing compounds having fungicidal properties (WO 95-04728).
It has already been disclosed that certain 3-(1-hydroxyphenyl-l-alkoximinomethyl)dioxazines can be prepared starting from the corresponding hydroxyphenyl-acetates (cf. WO 95-04728). Thus, for example (5,6-dihydro-1,4,2-dioxazin-3-yl)-(2-hydroxy-phenyl)-methanone O-methyl-oxime (1) is obtained by reacting methyl hydroxyphenylacetate (a) with dihydropyran, converting the dihydropyranyl ether (b) obtained in this way with t-butyl nitrite into methyl 2-[2-(tetrahydropyran-2-yloxy)phenyl]-2-hydroximino-acetate (c), alkylating this compound with iodomethane to give methyl 2-[2-(tetrahydropyran-2-yloxy)-phenyl]-2-methoximino-acetate (d), reacting this with hydroxylamine to give 2-[2-(tetrahydropyran-2-yloxy)-phenyl]-2-methoximino-N-hydroxyacetamide (e), cyclizing the latter with dibromoethane to 3-{1-[2-(tetrahydropyran-2-yloxy)-phenyl]-1-methoximino-methyl}-5,6-dihydro-1,2,4-dioxazine (f), and finally removing the tetrahydropyranyl group using acid catalysis. This synthesis can be illustrated by the following scheme: 
A major disadvantage of this process is the fact that it requires a large number of steps, some of which are of low yield, which significantly affects the profitability of this process.
It has now been found that 3-(1-hydroxyphenyl-1-alkoximinomethyl)dioxazines of the general formula 
in which
A represents alkyl,
R1, R2, R3 and R4 are identical or different and each represent independently of one another hydrogen, halogen, cyano, nitro, respectively optionally halogen-substituted alkyl, alkoxy, alkylthio, alkylsulphinyl or alkylsulphonyl, and
Z1, Z2, Z3 and Z4 are identical or different and each represent independently of one another hydrogen, alkyl, halogenoalkyl or hydroxyalkyl, or
Z1 and Z2 or Z1 and Z3 or Z3 and Z4 form together with the respective carbon atoms that they are attached to a cycloaliphatic ring,
are obtained when
a) O-hydroxyethyl-Oxe2x80x2-methyl-benzofurandione dioximes of the formula 
xe2x80x83in which
A, R1, R2, R3, R4, Z1, Z2, Z3 and Z4 are each as defined above,
are rearranged, if appropriate in the presence of a diluent and, if appropriate, in the presence of an acid or a base, or
b) hydroxybenzoyldioxazines of the formula 
xe2x80x83in which
R1, R2, R3, R4, Z1, Z2, Z3 and Z4 are each as defined above,
are reacted with an alkoxyamine of the formula
Axe2x80x94Oxe2x80x94NH2xe2x80x83xe2x80x83(IV)
xe2x80x83in which
A is as defined above
xe2x80x94or an acid addition complex thereofxe2x80x94
if appropriate in the presence of a diluent and, if appropriate, in the presence of an acid acceptor, or
c) hydroxyphenyl-hydroximinomethyl-dioxazines of the formula 
xe2x80x83in which
R1, R2, R3, R4, Z1, Z2, Z3 and Z4 are each as defined above,
are reacted with an alkylating agent of the formula
Axe2x80x94Xxe2x80x83xe2x80x83(VI)
xe2x80x83in which
A is as defined above, and
X represents halogen, alkylsulphonyloxy, alkoxysulphonyloxy or arylsulphonyloxy,
if appropriate in the presence of a diluent and, if appropriate, in the presence of a base.
In the definitions, the saturated or unsaturated hydrocarbon chains, such as alkyl also in connection with hetero atoms, such as in alkoxy or alkylthio, are in each case straight-chain or branched.
The methods of the processes a-c) according to the invention are preferably employed for preparing compounds of the formula (I) in which
A represents methyl, ethyl, n- or i-propyl,
R1, R2, R3 and R4 are identical or different and each represent independently of one another hydrogen, halogen, cyano or nitro, or represent alkyl, alkoxy, alkylthio, alkylsulphinyl or alkylsulphonyl, each of which is optionally substituted by 1 to 5 halogen atoms and each of which has 1 to 6 carbon atoms,
Z1, Z2, Z3 and Z4 are identical or different and each represent independently of one another hydrogen, alkyl or hydroxyalkyl having 1 to 4 carbon atoms or halogenoalkyl having 1 to 4 carbon atoms and 1 to 5 identical or different halogen atoms, or
Z1 and Z2 or Z1 and Z3 or Z3 and Z4 form together with the respective carbon atoms that they are attached to a cycloaliphatic ring having five, six or seven carbon atoms.
Particular preference is given to preparing compounds of the formula (1) in which
A represents methyl or ethyl,
R1, R2, R3 and R4 are identical or different and each represent independently of one another hydrogen, fluorine, chlorine, bromine, cyano, nitro, methyl, ethyl, n- or i-propyl, n-, i-, s- or t-butyl, methoxy, ethoxy, n- or i-propoxy, methylthio, ethylthio, methylsulphinyl, ethylsulphinyl, methylsulphonyl or ethylsulphonyl, trifluoromethyl, trifluoroethyl, difluoromethoxy, trifluoromethoxy, difluorochloromethoxy, trifluoroethoxy, difluoromethylthio, difluorochloromethylthio, trifluoromethylthio, trifluoromethylsulphinyl or trifluoromethylsulphonyl, and
Z1, Z2, Z3 and Z4 are identical or different and each represent independently of one another hydrogen, methyl, ethyl, n- or i-propyl, n-, i-, s- or t-butyl, hydroxymethyl, trifluoromethyl or trifluoroethyl, or
Z1 and Z2 or Z1 and Z3 or Z3 and Z4 form together with the respective carbon atoms that they are attached to a cycloaliphatic ring having five, six or seven carbon atoms.
The O-hydroxyethyl-Oxe2x80x2-methyl-benzofurandione dioximes required as starting materials in the practice of the process a) according to the invention are defined in a general way by the formula (II). In this formula (II), A, R1, R2, R3, R4, Z1, Z2, Z3 and Z4 preferably or particularly have those meanings already mentioned in connection with the description of the compounds of the formula (I) which can be prepared according to the invention as being preferred or particularly preferred for A, R1, R2, R3, R4, Z1, Z2, Z3 and Z4.
The starting materials of the formula (II) have not been disclosed before, and as novel compounds they also form part of the subject matter of the present application.
The O-hydroxyethyl-Oxe2x80x2-methyl-benzofurandione dioximes of the formula (II) are obtained when
process d) O-hydroxyethyl-benzofurandione monooximes of the formula 
xe2x80x83in which
R1, R2, R3, R4, Z1, Z2, Z3 and Z4 are each as defined above
are reacted with an alkoxyamine of the formula (IV)
xe2x80x94or an acid addition complex thereofxe2x80x94
if appropriate in the presence of a diluent and, if appropriate, in the presence of an acid acceptor, or
process e) O-alkyl-benzofurandione dioximes of the formula 
xe2x80x83in which
A, R1, R2, R3 and R4 are each as defined above
are reacted with an ethane derivative of the formula 
xe2x80x83in which
Y1 represents halogen, alkylsulphonyloxy, arylsulphonyloxy or alkanoyloxy, and
G represents hydrogen, or
Y1 and G are linked to each other by a single bond, where
Y1 represents oxygen and
G represents 
xe2x80x83or
Y1 and G together represent a single bond, and
Z1, Z2, Z3 and Z4 are each as defined above,
if appropriate in the presence of a diluent and, if appropriate, in the presence of a base, or
process f) O-hydroxyethyl-benzofurandione dioximes of the formula 
xe2x80x83in which
R1, R2, R3, R4, Z1, Z2, Z3 and Z4 are each as defined above
are reacted with an alkylating agent of the formula (VI),
if appropriate in the presence of a diluent and, if appropriate, in the presence of a base, or
process m) O-oxyethyl-Oxe2x80x2-methyl-benzofurandione dioximes of the formula 
xe2x80x83in which
A, R1, R2, R3, R4, Z1, Z2, Z3 and Z4 are each as defined above and
E represents an acyl group or a ketal protecting group,
are reacted with water or an alcohol, if appropriate in the presence of a diluent and, if appropriate, in the presence of an acid or a base.
The O-hydroxyethyl-benzofurandione monooximes required as starting materials in the practice of the process d) according to the invention are defined in a general way by the formula (VII). In this formula (VII), R1, R2, R3, R4, Z1, Z2, Z3 and Z4 preferably or particularly have those meanings already mentioned in connection with the description of the compounds of the formula (I) which can be prepared according to the invention as being preferred or particularly preferred for R1, R2, R3, R4, Z1, Z2, Z3 and Z4.
The starting materials of the formula (VII) have not been disclosed before, and as novel compounds they also form part of the subject matter of the present application.
The O-hydroxyethyl-benzofurandione monooximes of the formula (VII) are obtained
process g) benzofurandione monooximes of the formula 
xe2x80x83in which
R1, R2, R3 and R4 are each as defined above
are reacted with an ethane derivative of the formula (IX),
if appropriate in the presence of a diluent and, if appropriate, in the presence of a base, or
process n) O-oxyethyl-benzofurandione monooximes of the formula 
xe2x80x83in which
E, R1, R2, R3, R4, Z1, Z2, Z3 and Z4 are each as defined above
are reacted with water or an alcohol, if appropriate in the presence of a diluent and, if appropriate, in the presence of an acid or a base.
The benzofurandione monooximes required as starting materials in the practice of the process g) according to the invention are defined in a general way by the formula (XI). In this formula (XI), R1, R2, R3 and R4 preferably or particularly have those meanings already mentioned in connection with the description of the compounds of the formula (I) which can be prepared according to the invention as being preferred or particularly preferred for R1, R2, R3 and R4.
The benzofurandione monooximes of the formula (XI) are known and can be prepared by known methods (cf. Beilstein, E (II) 17, 462; Mameli, G. 56, 768; Chem. Ber. 35 (1902), 1640-1646; Proc. Indian Acad. Sci. Sect. A (1976) 83A(6), 238-242)).
The O-oxyethyl-benzofurandione monooximes required as starting materials in the practice of the process n) according to the invention are defined in a general way by the formula (XIV). In this formula (XIV), R1, R2, R3, R4, Z1, Z2, Z3 and Z4 preferably or particularly have those meanings already mentioned in connection with the description of the compounds of the formula (I) which can be prepared according to the invention as being preferred or particularly preferred for R1, R2, R3, R4, Z1, Z2, Z3 and Z1. E preferably or particularly has that meaning mentioned below in connection with the description of the compounds of the formula (XIII) according to the invention as being preferred or particularly preferred for E.
The starting materials of the formula (XIV) have not been disclosed before, and as novel compounds they also form part of the subject matter of the present application.
The O-oxyethyl-benzofurandione monooximes of the formula (XIV) are obtained when
process o) benzofurandione monooximes of the formula (XI) are reacted with an ethanol derivative of the formula 
xe2x80x83in which
E, Z1, Z2, Z3 and Z4 are each as defined above, and
Y2 represents halogen, alkylsulphonyloxy, arylsulphonyloxy or alkanoyloxy,
if appropriate in the presence of a diluent and, if appropriate. in the presence of an acid acceptor.
The benzofurandione monooximes of the formula (XI) required as starting materials in the practice of the process o) according to the invention have already been described in the description of the process g) according to the invention.
The O-alkyl-benzofurandione dioximes required as starting materials in the practice of the process e) according to the invention are defined in a general way by the formula (VIII). In this formula (VIII), R1, R2, R3 and R4 preferably or particularly have those meanings already mentioned in connection with the description of the compounds of the formula (I) which can be prepared according to the invention as being preferred or particularly preferred for R1, R2, R3 and R4.
The starting materials of the formula (VIII) have not been disclosed before, and as novel compounds they also form part of the subject matter of the present application.
The O-hydroxyethyl-benzofurandione monooximes of the formula (VIII) are obtained when
process h) benzofurandione monooximes of the formula (XI) are reacted with an alkoxyamine of the formula (IV),
if appropriate in the presence of a diluent and, if appropriate, in the presence of an acid acceptor, or
process p) benzofurandione dioximes of the formula 
xe2x80x83in which
R1, R2, R3 and R4 are each as defined above
are reacted with an alkylating agent of the formula (VI),
if appropriate in the presence of a diluent and, if appropriate, in the presence of a base.
The benzofurandione monooximes of the formula (XI) required as starting materials in the practice of the process h) according to the invention have already been described in the description of the process g) according to the invention.
The benzofurandione dioximes required as starting materials in the practice of the process p) according to the invention are defined in a general way by the formula (XII). In this formula (XII), R1, R2, R3 and R4 preferably or particularly have those meanings already mentioned in connection with the description of the compounds of the formula (I) which can be prepared according to the invention as being preferred or particularly preferred for R1, R2, R3 and R4.
The benzofurandione dioximes of the formula (XII) are known and can be prepared by known methods (cf. Chem. Ber. 42 (1909), 202).
The O-hydroxyethyl-benzofurandione dioximes required as starting materials in the practice of the process f) according to the invention are defined in a general way by the formula (X). In this formula (X), R1, R2, R3 and R4 preferably or particularly have those meanings already mentioned in connection with the description of the compounds of the formula (I) which can be prepared according to the invention as being preferred or particularly preferred for R1, R2, R3 and R4.
The starting materials of the formula (X) have not been disclosed before, and as novel compounds they also form part of the subject matter of the present application.
The O-hydroxyethyl-benzofurandione dioximes of the formula (X) are obtained when
process i) O-hydroxyethyl-benzofurandione monooximes of the formula (VII)
are reacted with hydroxylaminexe2x80x94or an acid addition complex thereofxe2x80x94
if appropriate in the presence of a diluent and, if appropriate, in the presence of an acid acceptor, or
process q) O-oxyethyl-benzofurandione dioximes of the formula 
xe2x80x83in which
E, R1, R2, R3, R4, Z1, Z2, Z3 and Z4 are each as defined above,
are reacted with water or an alcohol, if appropriate in the presence of a diluent and, if appropriate, in the presence of an acid or a base.
The O-hydroxyethyl-benzofurandione monooximes of the formula (VII) required as starting materials in the practice of the process i) according to the invention have already been described in the description of the process d) according to the invention.
The O-oxyethyl-benzofurandione dioximes required as starting materials in the practice of the process q) according to the invention are defined in a general way by the formula (XVI). In this formula (XVI), R1, R2, R3, R4, Z1, Z2, Z3 and Z4 preferably or particularly have those meanings already mentioned in connection with the description of the compounds of the formula (I) which can be prepared according to the invention as being preferred or particularly preferred for R1, R2, R3, R4, Z1, Z2, Z3 and Z4. E preferably or particularly has those meanings mentioned below in connection with the description of the compounds of the formula (XIII) according to the invention as being preferred or particularly preferred for E.
The starting materials of the formula (XVI) have not been disclosed before, and as novel compounds they also form part of the subject matter of the present application.
The O-oxyethyl-benzofurandione dioximes of the formula (XVI) are obtained when
process r) O-oxyethyl-benzofurandione monooximes of the formula (XIV)
are reacted with hydroxylaminexe2x80x94or an acid addition complex thereofxe2x80x94
if appropriate in the presence of a diluent and, if appropriate, in the presence of an acid acceptor.
The O-oxyethyl-benzofurandione monooximes of the formula (XIV) required as starting materials in the practice of the process r) according to the invention have already been described in the description of the process n) according to the invention.
The O-oxyethyl-Oxe2x80x2-methyl-benzofurandione dioximes of the formula (XIII) required as starting materials in the practice of the process m) according to the invention are defined in a general way by the formula (III). In this formula (XIII), A, R1, R2, R3, R4, Z1, Z2, Z3 and Z4 preferably or particularly have those meanings already mentioned in connection with the description of the compounds of the formula (I) which can be prepared according to the invention as being preferred or particularly preferred for A, R1, R2, R3, R4, Z1, Z2, Z3 and Z4. E represents an acyl group, preferably formyl, acetyl or benzoyl, or a ketal protecting group, preferably 2-tetrahydropyranyl, 1-methoxy-1-ethyl, 1-ethoxy-1-ethyl, methoxymethyl or ethoxymethyl.
The starting materials of the formula (XIII) have not been disclosed before, and as novel compounds they also form part of the subject matter of the present application.
The O-oxyethyl-Oxe2x80x2-methyl-benzofurandione dioximes of the formula (XIII) are obtained when
process s) O-oxyethyl-benzofurandione monooximes of the formula (XIV) are reacted with an alkoxyamine of the formula (IV)
xe2x80x94or an acid addition complex thereofxe2x80x94
if appropriate in the presence of a diluent and, if appropriate, in the presence of an acid acceptor, or
process t) O-oxyethyl-benzofurandione dioximes of the formula (XVI) are reacted with an alkylating agent of the formula (VI),
if appropriate in the presence of a diluent and, if appropriate, in the presence of a base, or
process u) O-alkyl-benzofurandione dioximes of the formula (VIII) are reacted with an ethanol derivative of the formula (XV),
if appropriate in the presence of a diluent and, if appropriate, in the presence of an acid acceptor.
The O-oxyethyl-benzofurandione monooximes of the formula (XIV) required as starting materials in the practice of the process s) according to the invention have already been described in the description of the process n) according to the invention.
The O-oxyethyl-benzofurandione dioximes of the formula (XVI) required as starting materials in the practice of the process t) according to the invention have already been described in the description of the process q) according to the invention.
The O-alkyl-benzofurandione dioximes of the formula (VIII) required as starting materials in the practice of the process u) according to the invention have already been described in the description of the process e) according to the invention.
The hydroxybenzoyldioxazines required as starting materials in the practice of the process b) according to the invention are defined in a general way by the formula (III). In this formula (III), R1, R2, R3, R4, Z1, Z2, Z3 and Z4 preferably or particularly have those meanings already mentioned in connection with the description of the compounds of the formula (I) which can be prepared according to the invention as being preferred or particularly preferred for R1, R2, R3, R4, Z1, Z2, Z3 and Z4.
The starting materials of the formula (III) have not been disclosed before, and as novel compounds they also form part of the subject matter of the present application.
The hydroxybenzoyldioxazines of the formula (III) are obtained when
process k) O-hydroxyethyl-benzofurandione monooximes of the formula (VII)
are reacted, if appropriate in the presence of a diluent and, if appropriate, in the presence of an acid or a base.
The O-hydroxyethyl-benzofurandione monooximes of the formula (VII) required as starting materials in the practice of the process k) according to the invention have already been described in the description of the process d) according to the invention.
The hydroxyphenyl-hydroximinomethyl-dioxazines required as starting materials in the practice of the process c) according to the invention are defined in a general way by the formula (V). In this formula (V), R1, R2, R3, R4, Z1, Z2, Z3 and Z4 preferably or particularly have those meanings already mentioned in connection with the description of the compounds of the formula (I) which can be prepared according to the invention as being preferred or particularly preferred for R1, R2, R3, R4, Z1, Z2, Z3 and Z4.
The starting materials of the formula (V) have not been disclosed before, and as novel compounds they also form part of the subject matter of the present application.
The hydroxyphenyl-hydroximinomethyl-dioxazines of the formula (V) are obtained when
process l) hydroxybenzoyldioxazines of the formula (III)
are reacted with hydroxylaminexe2x80x94or an acid addition complex thereofxe2x80x94
if appropriate in the presence of a diluent and, if appropriate, in the presence of an acid acceptor, or
process v) O-hydroxyethyl-benzofurandione dioximes of the formula (X)
are rearranged, if appropriate in the presence of a diluent and, if appropriate, in the presence of an acid or a base.
The hydroxybenzoyldioxazines of the formula (III) required as starting materials in the practice of the process l) according to the invention have already been described in the description of the process b) according to the invention.
The O-hydroxyethyl-benzofurandione dioximes of the formula (X) required as starting materials in the practice of the process v) according to the invention have already been described in the description of the process f) according to the invention.
The alkoxyamines further required as starting materials in the practice of the processes b), d), h) and s) according to the invention are defined in a general way by the formula (IV). In this formula (IV), A preferably or particularly has that meaning already mentioned in connection with the description of the compounds of the formula (I) which can be prepared according to the invention as being preferred or particularly preferred for A. Preferred acid addition complexes of the alkoxyamines of the formula (IV) are their hydrochlorides, sulphates and hydrogen sulphates.
The alkoxyamines of the formula (IV) and their acid addition complexes are known chemicals for synthesis.
The alkylating agents further required as starting materials in the practice of the processes c), f), p) and t) according to the invention are defined in a general way by the formula (VI). In this formula (VI), A preferably or particularly has that meaning already mentioned in connection with the description of the compounds of the formula (I) which can be prepared according to the invention as being preferred or particularly preferred for A. X represents halogen, preferably chlorine, bromine or iodine, alkylsulphonyloxy, preferably methylsulphonyloxy, alkoxysulphonyloxy, preferably methoxysulphonyloxy, or arylsulphonyloxy, preferably 4-tolylsulphonyloxy.
The alkylating agents of the formula (VI) are known chemicals for synthesis.
The ethane derivatives further required as starting materials in the practice of the processes e) and g) according to the invention are defined in a general way by the formula (IX). In this formula (IX), Z1, Z2, Z3 and Z4 preferably or particularly have those meanings already mentioned in connection with the description of the compounds of the formula (I) which can be prepared according to the invention as being preferred or particularly preferred for Z1, Z2, Z3 and Z4. Y1 represents halogen, preferably chlorine, bromine or iodine, alkylsulphonyloxy, preferably methylsulphonyloxy, arylsulphonyloxy, preferably 4-tolylsulphonyloxy, or alkanoyloxy, preferably acetyloxy. G represents hydrogen or is linked to Y1 by a single bond, Y1 being oxygen and G being carbonyl, or else G together with Y1 represent a single bond.
The ethane derivatives of the formula (IX) are known chemicals for synthesis.
The hydroxylamine further required as starting material in the practice of the processes i), l) and r) according to the invention, or its acid addition complexes, preferably its hydrochloride, sulphate and hydrogen sulphate, are known chemicals for synthesis.
The ethanol derivatives further required as starting materials in the practice of the processes o) and u) according to the invention are defined in a general way by the formula (XV). In this formula (XV), Z1, Z2, Z3 and Z4 preferably or particularly have those meanings already mentioned in connection with the description of the compounds of the formula (I) which can be prepared according to the invention as being preferred or particularly preferred for Z1, Z2, Z3 and Z4. E preferably or particularly has that meaning already mentioned in connection with the description of the compounds of the formula (XIII) according to the invention as being preferred or particularly preferred for E. Y2 represents halogen, preferably chlorine, bromine or iodine, alkylsulphonyloxy, preferably methylsulphonyloxy, arylsulphonyloxy, preferably 4-tolylsulphonyloxy, or alkanoyloxy, preferably acetyloxy.
The ethanol derivatives of the formula (XV) are known and can be prepared by known methods (cf. for example Newkome, George R.; Marston, Charles R., J. Org. Chem., 50, 22, 1985, 4238-4245; Henry, Chem. Ber., 7  less than 1874 greater than , 70).
If the processes a), k) and v) according to the invention are carried out in the presence of an acid, suitable diluents are all inert organic solvents. These preferably include aliphatic, alicyclic or aromatic hydrocarbons, such as, for example, petroleum ether, hexane, heptane, cyclohexane, methylcyclohexane, benzene, toluene, xylene or decalin; halogenated hydrocarbons, such as, for example, chlorobenzene, dichlorobenzene, dichloromethane, chloroform, carbon tetrachloride, dichloroethane or trichloroethane; ethers, such as diethyl ether, diisopropyl ether, dioxane, 1,2-dimethoxyethane, 1,2-diethoxyethane or anisole; esters, such as methyl acetate or ethyl acetate, or sulphones, such as sulpholane, and also any mixtures of the diluents mentioned. Particularly preferred diluents are ethers, such as diethyl ether, 1,2-diethoxyethane or anisole; and aromatic hydrocarbons, such as, for example, benzene, toluene or xylene.
If the processes a), k) and v) according to the invention are carried in the presence of a base, suitable diluents are water and all organic solvents. These preferably include aliphatic, alicyclic or aromatic hydrocarbons, such as, for example, petroleum ether, hexane, heptane, cyclohexane, methylcyclohexane, benzene, toluene, xylene or decalin; halogenated hydrocarbons, such as, for example, chlorobenzene, dichlorobenzene, dichloromethane, chloroform, carbon tetrachloride, dichloroethane or trichloroethane; ethers, such as diethyl ether, diisopropyl ether, methyl t-butyl ether, methyl t-amyl ether, dioxane, tetrahydrofuran, 1,2-dimethoxyethane, 1,2-diethoxyethane or anisole; nitriles, such as acetonitrile, propionitrile, n- or i-butyronitrile or benzonitrile; amides, such as N,N-dimethylformamide, N,N-dimethylacetamide, N-methylformanilide, N-methylpyrrolidone or hexamethylphosphoric triamide; esters, such as methyl acetate or ethyl acetate, sulphoxides, such as dimethyl sulphoxide; sulphones, such as sulpholane; alcohols, such as methanol, ethanol, n- or i-propanol, n-, i-, sec- or tert-butanol, ethanediol, propane-1,2-diol, ethoxyethanol, methoxyethanol, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, and their mixtures with water. Preferred diluents are water, alcohols, such as methanol, ethanol, n- or i-propanol, n-, i-, sec- or tert-butanol, ethanediol, propane-1,2-diol, ethoxyethanol, methoxyethanol, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether; and their mixtures with water. Particularly preferred diluents in this instance are water or alcohols, such as methanol, ethanol, n- or i-propanol, n-, i-, sec- or tert-butanol, ethanediol, propane-1,2-diol, ethoxyethanol, methoxyethanol, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, and their mixtures with water.
Suitable diluents in the practice of the processes b), d), h), i), l), r) and s) according to the invention are all inert organic solvents. These preferably include aromatic hydrocarbons, such as, for example, benzene, toluene or xylene; halogenated hydrocarbons, such as, for example, chlorobenzene, dichlorobenzene, dichloromethane, chloroform, carbon tetrachloride, dichloroethane or trichloroethane; ethers, such as diethyl ether, diisopropyl ether, methyl t-butyl ether, methyl t-amyl ether, dioxane, tetrahydrofuran, 1,2-dimethoxyethane, 1,2-diethoxyethane or anisole; amides, such as N,N-dimethylformamide, N,N-dimethylacetamide, N-methylformanilide, N-methylpyrrolidone or hexamethylphosphoric triamide; organic acids, such as acetic acid; esters, such as methyl acetate or ethyl acetate; sulphoxides, such as dimethyl sulphoxide; sulphones, such as sulpholane; alcohols, such as methanol, ethanol, n- or i-propanol, n-, i-, sec- or tert-butanol, ethanediol, propane-1,2-diol, ethoxyethanol, methoxyethanol, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, their mixtures with water or pure water. Particularly preferred diluents are amides, such as N,N-dimethylformamide, N,N-dimethylacetamide, N-methylformanilide, N-methylpyrrolidone or hexamethylphosphoric triamide; alcohols, such as methanol, ethanol, n- or i-propanol, n-, i-, sec- or tert-butanol, ethanediol, propane-1,2-diol, ethoxyethanol, methoxyethanol, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, acids, such as acetic acid, their mixtures with water or pure water. Further particular preference is also given to two-phase mixtures, such as, for example, water/toluene.
Suitable diluents in the practice of the processes c), e), f), g), o), p), t) and u) according to the invention are all inert organic solvents. These preferably include aliphatic, alicyclic or aromatic hydrocarbons, such as, for example, petroleum ether, hexane, heptane, cyclohexane, methylcyclohexane, benzene, toluene, xylene or decalin; halogenated hydrocarbons, such as, for example, chlorobenzene, dichlorobenzene dichloromethane, chloroform, carbon tetrachloride, dichloroethane or trichloroethane; ethers, such as diethyl ether, diisopropyl ether, methyl t-butyl ether, methyl t-amyl ether, dioxane, tetrahydrofuran, 1,2-dimethoxyethane, 1,2-diethoxyethane or anisole; ketones, such as acetone, butanone, methyl isobutyl ketone or cyclohexanone, nitriles, such as acetonitrile, propionitrile, n- or i-butyronitrile or benzonitrile; amides, such as N,N-dimethylformamide, N,N-dimethylacetamide, N-methylformanilide, N-methylpyrrolidone or hexamethylphosphoric triamide; esters, such as methyl acetate or ethyl acetate; sulphoxides, such as dimethyl sulphoxide, sulphones, such as sulpholane; alcohols, such as methanol, ethanol, n- or i-propanol, n-, i-, sec- or tert-butanol, ethanediol, propane-1,2-diol, ethoxyethanol, methoxyethanol, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, their mixtures with water or pure water. Particularly preferred diluents are ketones, such as acetone, butanone, methyl isobutyl ketone or cyclohexanone; nitriles, such as acetonitrile, propionitrile, n- or i-butyronitrile or benzonitrile; amides, such as N,N-dimethylformamide, N,N-dimethylacetamide, N-methylformanilide, N-methylpyrrolidone or hexamethylphosphoric triamide; alcohols, such as methanol, ethanol, n- or i-propanol, n-, i-, sec- or tert-butanol, ethanediol, propane-1,2-diol, ethoxyethanol, methoxyethanol, diethylene glycol monomethyl ether or diethylene glycol monoethyl ether. Further particular preference is also given to two-phase mixtures, such as, for example, water/toluene.
Suitable diluents in the practice of the processes m), n) and q) according to the invention are water and all organic solvents. These preferably include ethers, such as diethyl ether, diisopropyl ether, methyl t-butyl ether, methyl t-amyl ether, dioxane, tetrahydrofuran, 1,2-dimethoxyethane, 1,2-diethoxyethane or anisole; ketones, such as acetone, butanone, methyl isobutyl ketone or cyclohexanone; nitriles, such as acetonitrile, propionitrile, n- or i-butyronitrile or benzonitrile; amides, such as N,N-dimethylformamide, N,N-dimethylacetamide, N-methylformanilide, N-methylpyrrolidone or hexamethylphosphoric triamide, esters, such as methyl acetate or ethyl acetate; sulphoxides, such as dimethyl sulphoxide; sulphones, such as sulpholane; alcohols, such as methanol, ethanol, n- or i-propanol, n-, i-, sec- or tert-butanol, ethanediol, propane-1,2-diol, ethoxyethanol, methoxyethanol, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, their mixtures with water or pure water.
The processes a), k) and v) according to the invention are, if appropriate, carried out in the presence of an acid or a base. Suitable acids include all inorganic or organic protic and Lewis acids, and also all polymeric acids. These include, for example, hydrogen chloride, hydrogen bromide, sulphuric acid, formic acid, acetic acid, trifluoroacetic acid, methanesulphonic acid, trifluoromethanesulphonic acid, toluenesulphonic acid, boron trifluoride (also as etherate), boron tribromide, aluminum trichloride, zinc chloride, iron(III) chloride, antimony pentachloride, acid ion exchangers, acid clays and acid silica gel. Preference is given to hydrogen chloride or hydrogen bromide. Suitable bases include common inorganic or organic bases. These preferably include alkaline earth metal or alkali metal hydrides, hydroxides, amides, alkoxides, acetates, carbonates or bicarbonates, such as, for example, sodium hydride, sodium amide, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydroxide, potassium hydroxide, ammonium hydroxide, sodium acetate, potassium acetate, calcium acetate, ammonium acetate, sodium carbonate, potassium carbonate, potassium bicarbonate, sodium bicarbonate or ammonium carbonate, and tertiary amines, such as trimethylamine, triethylamine, tributylamine, N,N-dimethylaniline, N,N-dimethyl-benzylamine, pyridine, N-methylpiperidine, N-methylmorpholine, N,N-dimethylaminopyridine, diazabicyclooctane (DABCO), diazabicyclononene (DBN) or diazabicycloundecene (DBU). Particularly preferred bases are sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydroxide, potassium hydroxide, ammonium hydroxide, and tertiary amines, such as trimethylamine, triethylamine, tributylamine, N,N-dimethylaniline, N,N-dimethylbenzylamine, pyridine, N-methylpiperidine, N-methylmorpholine, N,N-dimethylaminopyridine, diazabicyclooctane (DABCO), diazabicyclononene (DBN) or diazabicycloundecene (DBU).
If appropriate, the processes b), d), h), i), l), r) and s) according to the invention are carried out in the presence of a suitable acid acceptor. These include all common inorganic or organic bases. They preferably include alkaline earth metal or alkali metal hydroxides, alkoxides, acetates, carbonates or bicarbonates, such as, for example, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydroxide, potassium hydroxide, ammonium hydroxide, sodium acetate, potassium acetate, calcium acetate, ammonium acetate, sodium carbonate, potassium carbonate, potassium bicarbonate, sodium bicarbonate or ammonium carbonate, and tertiary amines, such as trimethylamine, triethylamine, tributylamine, N,N-dimethylaniline, N,N-dimethylbenzylamine, pyridine, N-methylpiperidine, N-methylmorpholine, N,N-dimethylaminopyridine, diazabicyclooctane (DABCO), diazabicyclononene (DBN) or diazabicycloundecene (DBU).
If appropriate, the processes c), e), f), g), o), p), t) and u) are carried out in the presence of a suitable acid acceptor. These are all common inorganic or organic bases. These preferably include alkaline earth metal or alkali metal hydrides, hydroxides, amides, alkoxides, carbonates or bicarbonates, such as, for example, sodium hydride, sodium amide, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, potassium bicarbonate or sodium bicarbonate, and tertiary amines, such as trimethylamine, triethylamine, tributylamine, N,N-dimethylaniline, N,N-dimethyl-benzylamine, pyridine, N-methylpiperidine, N-methylmorpholine, N,N-dimethylaminopyridine, diazabicyclooctane (DABCO), diazabicyclononene (DBN) or diazabicycloundecene (DBU).
In the practice of the processes a), k) and v) according to the invention, the reaction temperatures may be varied over a relatively wide range. The reactions are generally carried out at temperatures from xe2x88x9220xc2x0 C. to 100xc2x0 C., preferably at temperatures from xe2x88x9210xc2x0 C. to 80xc2x0 C.
In the practice of the processes b), d), h), i), l), r) and s) according to the invention, the reaction temperatures may be varied over a relatively wide range. The reactions are generally carried out at temperatures from 0xc2x0 C. to 200xc2x0 C., preferably at temperatures from 20xc2x0 C. to 150xc2x0 C.
In the practice of the processes c), e), f), g), o), p), t) and u) according to the invention, the reaction temperatures may be varied over a relatively wide range. The reactions are generally carried out at temperatures from xe2x88x9220xc2x0 C. to 100xc2x0 C., preferably at temperatures from 0xc2x0 C. to 80xc2x0 C.
The processes a) to v) according to the invention are generally carried out at atmospheric pressure. However, it is also possible to carry out the processes at elevated or reduced pressurexe2x80x94in general between 0.1 bar and 10 bar.
In a preferred process variant (A), a benzofurandione monooxime of the formula (XI) is initially converted into an O-hydroxyethyl-benzofurandione monooxime of the formula (VII) by reaction with an ethane derivative of the formula (IX), as described in process g). Without further purification, this is then reacted with an alkoxyamine of the formula (IV)xe2x80x94or an acid addition complex thereofxe2x80x94if appropriate in a buffer system such as, for example, sodium acetate/acetic acid as described in process d), to afford an O-hydroxyethyl-Oxe2x80x2-methyl-benzofurandione dioxime of the formula (II) which, in turn, yields the desired 3-(1-hydroxyphenyl-1-alkoximinomethyl)dioxazine of the formula (I) without further purification on treatment with an acid or a base by the method of process a).
In a further preferred process variant (B), a benzofurandione monooxime of the formula (XI) is initially converted into an O-hydroxyethyl-benzofurandione monooxime of the formula (VII) by reaction with an ethane derivative of the formula (IX), as described in process g). Upon treatment with an acid or base, this affords a hydroxybenzoyldioxazine of the formula (III) which is then reacted with an alkoxyamine of the formula (V)xe2x80x94or an acid addition complex thereofxe2x80x94to give the desired 3-(1-hydroxyphenyl-1-alkoximinomethyl)dioxazine of the formula (I).
In a third preferred process variant (C), a benzofurandione monooxime of the formula (XI) is initially converted into an O-alkyl-benzofurandione dioxime of the formula (VIII) by reaction with an alkoxyamine of the formula (IV)xe2x80x94or an acid addition complex thereof. This is then reacted with an ethane derivative of the formula (IX) to afford an O-hydroxyethyl-Oxe2x80x2-methyl-benzofurandione dioxime of the formula (II) which on treatment with an acid or a base yields the desired 3-(1-hydroxyphenyl-1-alkoximinomethyl)dioxazine of the formula (I).
It is very surprising that the processes according to the invention, in particular when combined, yield high purity products in high yields. Chem. Ber. 1902, 1640, for example, describes that benzofurandione monooximes of the formula (XI) are cleaved to give salicylic acid derivatives or hydroxyphenylglyoxylic acid derivatives by treatment with acids and with bases. It was therefore unforeseeable that the 3-(1-hydroxyphenyl-1-alkoximinomethyl)dioxazines can be prepared without any significant side reactions in a reaction comprising only three steps.
The processes according to the invention have a number of advantages. They allow, for example, the preparation of a large quantity of 3-(1-hydroxyphenyl-1-alkoximinomethyl)dioxazines in high yields and high purities. It is a further advantage that the benzofurandione monooximes required as starting materials are obtainable in a simple manner even in major amounts (Beilstein, E (II) 17, 462; Mameli, G. 56, 768).